Emergence of Mammalian Species-Infectious and -Pathogenic Avian Influenza H6N5 Virus with No Evidence of Adaptation

Abstract

The migratory waterfowl of the world are considered to be the natural reservoir of influenza A viruses. Of the 16 hemagglutinin subtypes of avian influenza viruses, the H6 subtype is commonly perpetuated in its natural hosts and is of concern due to its potential to be a precursor of highly pathogenic influenza viruses by reassortment. During routine influenza surveillance, we isolated an unconventional H6N5 subtype of avian influenza virus. Experimental infection of mice revealed that this isolate replicated efficiently in the lungs, subsequently spread systemically, and caused lethality. The isolate also productively infected ferrets, with direct evidence of contact transmission, but no disease or transmission was seen in pigs. Although the isolate possessed the conserved receptor-binding site sequences of avian influenza viruses, it exhibited relatively low replication efficiencies in ducks and chickens. Our genetic and molecular analyses of the isolate revealed that its PB1 sequence showed the highest evolutionary relationship to those of highly pathogenic H5N1 avian influenza viruses and that its PA protein had an isoleucine residue at position 97 (a representative virulence marker). Further studies will be required to examine why our isolate has the virologic characteristics of mammalian influenza viruses but the archetypal receptor binding profiles of avian influenza viruses, as well as to determine whether its potential virulence markers (PB1 analogous to those of H5N1 viruses or isoleucine residue at position 97 within PA) could render it highly pathogenic in mice.

Complete Genome Sequence of a Mammalian Species-Infectious and -Pathogenic H6N5 Avian Influenza Virus without Evidence of Adaptation

“…The A/aquatic bird/Korea/ CN5/2009 (H6N5) [A/AB/Kor/CN5/09 (H6N5)] strain was isolated from fecal swabs of aquatic birds in 2009. Surprisingly, it showed infectivity and pathogenicity in mammalian species without evidence of adaptation (6). To date, primers targeting the noncoding regions (NCRs) have generally been used to obtain complete genomes of influenza A viruses.…”

H6 Influenza Viruses Pose a Potential Threat to Human Health

“…Although the H6 viruses isolated to date have largely caused asymptomatic infections in waterfowl, infection of chickens with H6 viruses has been associated with decreased egg production, upper respiratory tract infection, morbidity, and increased mortality (10)(11)(12)(13). Several studies have shown that certain H6 viruses can infect and cause illness in mice and ferrets (26,27). An H6N6 virus was also detected in pigs in Guangdong province in China in 2010 (28), and an H6N1 virus was isolated from a human with flu-like symptoms in Taiwan in 2013 (29).…”

Experimental evidence in support of single host maintenance of a multihost pathogen

“…The result of these evolutionary dynamics can manifest as decreased parasitism and virulence in the initial host species and increased virulence in new hosts (Ebert 1998). Introduction need not lead to increased pathogen specialization, though, since coevolution can also favour generalist strategies (Hall et al 2011) and host-switching does not always require adaptation by the pathogen (Nam et al 2011).…”